Transcript Routes of Drug Administration

Routes of Drug
Administration
Robert L. Copeland, Ph.D.
Department of Pharmacology
www.med.howard.edu/pharmacology
202.806.6311
Drug Absorption
 Absorption
is the process by
which a drug enters the
bloodstream without being
chemically altered or
 The movement of a drug
from its site of application
into the blood or lymphatic
system
Drug Absorption

Factors which influence the rate of
absorption
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types of transport
the physicochemical properties of the
drug
protein binding
routes of administration
dosage forms
circulation at the site of absorption
concentration of the drug
Drug Absorption

The rate at which a drug
reaches it site of action depends
on:
 Absorption - involves the
passage of the drug from its
site of administration into the
blood
 Distribution - involves the
delivery of the drug to the
tissues
Drug Absorption
 Mechanisms
of solute
transport across membranes

passive diffusion
filtration and bulk flow
endocytosis
ion-pairing
active transport
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Drug Absorption animation
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Ion Trapping cont:
Body fluids where a pH difference from
blood pH will favor trapping or
reabsorption: stomach contents
small intestine
breast milk
aqueous humor (eye)
vaginal secretions
prostatic secretions
Ion Trapping:
Kidney:
Nearly all drugs filtered at the glomerulus:
Most drugs in a lipid-soluble form will be absorbed
by passive diffusion.
To increase excretion: change the urinary pH to favor
the charged form of the drug:
• Weak acids: excreted faster in alkaline pH (anion
form favored)
• Weak bases: excreted faster in acidic pH (cation
form favored)
Lipid-Water Partition Coefficient
 The
ratio of the concentration
of the drug in two immiscible
phases: a nonpolar liquid or
organic solvent (representing
the
membrane);
and
an
aqueous
buffer,
pH
7.4
(representing the plasma)
Lipid-Water Partition Coefficient
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The higher the lipid/water p.c. the
greater the rate of transfer across
the membrane
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polarity of a drug, by increasing
ionization will
the lipid/ water p.c.
polarity of a drug, suppression of
ionization will
the lipid/ water p.c.
Routes of Drug
Administration
Important
Info
The route of administration
(ROA) that is chosen may have
a profound effect upon the
speed and efficiency with
which the drug acts
 The
possible routes of drug
entry into the body may be
divided into two classes:
Enteral
Parenteral
Enteral Routes
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Enteral - drug placed directly in the GI
tract:
 sublingual
- placed under the
tongue
 oral - swallowing (p.o., per os)
 rectum - Absorption through the
rectum
Sublingual/Buccal
Some drugs are taken as smaller
tablets which are held in the mouth
or under the tongue.
 Advantages
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rapid absorption
drug stability
avoid first-pass effect
Sublingual/Buccal
 Disadvantages
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inconvenient
small doses
unpleasant taste of some drugs
Oral
 Advantages
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Convenient - can be self- administered,
pain free, easy to take
Absorption - takes place along the whole
length of the GI tract
Cheap - compared to most other
parenteral routes
Oral
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Disadvantages
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Sometimes inefficient - only part
of the drug may be absorbed
First-pass effect - drugs
absorbed orally are initially
transported to the liver via the
portal vein
irritation to gastric mucosa nausea and vomiting
Oral
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Disadvantages cont.
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destruction of drugs by gastric
acid and digestive juices
effect too slow for emergencies
unpleasant taste of some drugs
unable to use in unconscious
patient
First-pass Effect
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The first-pass effect is the term
used for the hepatic metabolism
of a pharmacological agent when
it is absorbed from the gut and
delivered to the liver via the
portal circulation.
The greater
the first-pass effect, the less the
agent will reach the systemic
circulation when the agent is
administered orally
First-pass Effect cont.
Magnitude of first pass hepatic effect:
Extraction ratio (ER)
ER = CL liver / Q ; where Q is hepatic
blood flow (usually about 90 L per hour.
Systemic drug bioavailability (F) may be
determined from the extent of absorption
(f) and the extraction ratio (ER):
F = f x (1 -ER)
First-pass Effect
Rectal
1. unconscious patients and children
2. if patient is nauseous or vomiting
3. easy to terminate exposure
4. absorption may be variable
5. good for drugs affecting the bowel such
as laxatives
6. irritating drugs contraindicated
Parenteral Routes
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Intravascular (IV, IA)- placing a drug
directly into the blood stream
Intramuscular (IM) - drug injected into
skeletal muscle
Subcutaneous - Absorption of drugs
from the subcutaneous tissues
Inhalation - Absorption through the
lungs
Intravascular
Absorption phase is bypassed
(100% bioavailability)
1.precise, accurate and almost immediate onset of
action,
2. large quantities can be given, fairly pain free
3. greater risk of adverse effects
a. high concentration attained rapidly
b. risk of embolism
c. OOPS factor or !@#$%
Intramuscular
1. very rapid absorption of drugs in aqueous
solution
2.repository and slow release preparations
3.pain at injection sites for certain drugs
Subcutaneous
1. slow and constant absorption
2. absorption is limited by blood flow,
affected if circulatory problems exist
3. concurrent administration of
vasoconstrictor will slow absorption
Inhalation
1.gaseous and volatile agents and aerosols
2.rapid onset of action due to rapid access to
circulation
a.large surface area
b.thin membranes separates alveoli from
circulation
c.high blood flow
Particles larger than 20 micron and the particles impact
in the mouth and throat. Smaller than 0.5 micron and
they aren't retained.
Inhalation cont.
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Respiratory system. Except for IN, risk hypoxia.
Intranasal (snorting) Snuff, cocaine may be partly oral via postnasal dripping. Fairly fast to brain, local damage to septum.
Some of the volatile gases also appear to cross nasal membranes.
Smoke (Solids in air suspension, vapors) absorbed across lung
alveoli: Nicotine, opium, THC, freebase and crack cocaine,
crystal meth.Particles or vapors dissolve in lung fluids, then
diffuse. Longer action than volatile gases. Tissue damage from
particles, tars, CO.
Volatile gases: Some anaesthetics (nitrous oxide, ether) [precise
control], petroleum distillates. Diffusion and exhalation
(alcohol).
Lung-based transfer may get drug to brain in as little as five
seconds.
Topical
•Mucosal membranes (eye drops, antiseptic,
sunscreen, callous removal, nasal, etc.)
•Skin
a. Dermal - rubbing in of oil or ointment
(local action)
b. Transdermal - absorption of drug through
skin (systemic action)
i. stable blood levels
ii. no first pass metabolism
iii. drug must be potent or patch
becomes to large
Route for administration
-Time until effect
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intravenous 30-60 seconds
intraosseous 30-60 seconds
endotracheal 2-3 minutes
inhalation 2-3 minutes
sublingual 3-5 minutes
intramuscular 10-20 minutes
subcutaneous 15-30 minutes
rectal 5-30 minutes
ingestion 30-90 minutes
transdermal (topical) variable (minutes to
hours)
Time-release preparations
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Oral - controlled-release, timedrelease, sustained-release
 designed to produce slow,uniform
absorption for 8 hours or longer
 better compliance, maintain effect
over night, eliminate extreme peaks
and troughs
Time-release preparations
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Depot or reservoir preparations
- parental administration (except
IV), may be prolonged by using
insoluble salts or suspensions in
non-aqueous vehicles.
Important
Info
The ROA is determined by the
physical characteristics of the
drug, the speed which the drug is
absorbed and/ or released, as well
as the need to bypass hepatic
metabolism and achieve high
conc. at particular sites
No single method of drug
administration is ideal for all
drugs in all circumstances
THAT’S IT!!